title: Postmortem redistribution of fentanyl in the rabbit blood.
abstract: Postmortem redistribution of fentanyl in the rabbit was investigated after application of the 50-μg/h Durogesic pain patch. Patches were applied for 48 hours. Two cycles of patch administration were used before characterization of the postmortem redistribution. Fentanyl showed marked redistribution into the femoral and pulmonary veins of the rabbit through 48 hours after the animals were humanely killed and the pain patches removed. The plasma concentration of 2.34 ng/mL in the femoral blood before killing the animals increased 5.6-fold by 48 hours after patch removal to 13.2 ng/mL. This postmortem concentration is approximately 3-fold the C(max) determined during antemortem pharmacokinetic analysis, 4 ng/mL, which was achieved 24 hours after the application of the second 50-μg/h Durogesic pain patch. After blood sampling for 48 hours after animal termination with patch removal compared with sampling for 48 hours from animals not terminated and with patch removal, the exposure ratios in the terminated animals were approximately 30-fold, indicating that between the postmortem redistribution of fentanyl and the cessation of hepatic clearance of fentanyl in the rabbit, the postmortem redistribution of fentanyl leads to an elevated measures of postmortem blood concentrations relative to antemortem blood concentrations.
authors.affiliation: Department of Toxicology, Dermato-Cosmetology and Pharmacognosy, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium. lceelen@vub.ac.be
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Ceelen
authors.forename: Loeckie
authors.initials: L
authors.lastname: De Zwart
authors.forename: Marieke
authors.initials: M
authors.lastname: Voets
authors.forename: Vera
authors.initials: V
authors.lastname: Hillewaert
authors.forename: Johan
authors.initials: J
authors.lastname: Monbaliu
authors.forename: Greet
authors.initials: G
authors.lastname: Teuns
authors.forename: Werner
authors.initials: W
authors.lastname: Coussement
authors.forename: Tony
authors.initials: T
authors.lastname: Greway
mesh_terms: D000279:Administration, Cutaneous; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D000818:Animals; D002853:Chromatography, Liquid; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D053593:Forensic Toxicology; D016014:Linear Models; D013058:Mass Spectrometry; D011180:Postmortem Changes; D011817:Rabbits; D011897:Random Allocation
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl